Burning Mouth Syndrome: Pathophysiology, Investigations and Management- a Review

Acta Scientific Dental Sciences Volume 2 Issue 4 April 2018 Review Article

Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review

Papa Abdou Lecor1*, Mamadou Lamine Ndiaye2, Mamadou Lamine Guirassy3, Oumar Harouna Sall1 and Babacar Toure4 1Oral Physiology Service, Department of Odontology, Faculty of Medicine, Pharmacy and Odontology (FMPO), Cheikh Anta Diop University, Dakar, Senegal 2Dento-Maxillofacial Radiology Service, Department of Odontology, Faculty of Medicine, Pharmacy and Odontology (FMPO), Cheikh Anta Diop University, Dakar, Senegal 3Periodontology Service, Department of Odontology, Faculty of Medicine, Pharmacy and Odontology (FMPO), Cheikh Anta Diop University, Dakar, Senegal 4Consevative Dentistry and Endodontics Service, Department of Odontology, Faculty of Medicine, Pharmacy and Odontology (FMPO) Cheikh Anta Diop University, Dakar, Senegal

*Corresponding Author: Papa Abdou Lecor, Oral Physiology Service, Department of Odontology, Faculty of Medicine, Pharmacy and Odontology (FMPO), Cheikh Anta Diop University, Dakar, Senegal.

Received: January 16, 2018; Published: March 20, 2018

Abstract Burning Mouth Syndrome (BMS), or idiopathic stomatodynia, is a chronic debilitating oral condition characterized by a burning sensation of the oral mucosa in an apparently normal person. Its etiology and pathogenesis remain unclear. However, psychophysi- cal and neurophysiological studies highlight peripheral and central neuropathic sensory alterations rather than psychogenic factors.

available treatments are not very effective and focus on relieving symptoms and improving the quality of life. In order to improve Dysgeusia and xerostomia are often associated with sensory and somatosensory disorders suggesting a multifactorial etiology. The treatment outcomes, a better understanding of the pathophysiology of this syndrome could provide a basis for the development of more effective management strategies. This article reviews current knowledge of the pathophysiology, diagnosis, and management of BMS. Keywords: Neuropathic Pain; Stomatodynia; Glossodynia; Dysgeusia; Xerostomia; Review

Abbreviations varies according to the groups considered. It increases in women, about 7 women to 1 man and with age [7,9]. The occurrence is BMS: Burning Mouth Syndrome; IHS: International Headache - women with anti-depressive comorbidity. Prevalence rates of up ated Hemoglobin; TRPV1: Transient Receptor Potential Vanilloid rare before age 30 and the most exposed group is postmenopausal Society; GRED: Gastroesophageal Reflux Disease; A1C: Glycosyl 1; P2X3: Purinergic Receptors Phenotypes P2X; PROP: 6-n-Propyl- women and psychiatric patients [10]. In Africa, few studies car- thiouracil; VAS: Visual Analog Scale; OHIP: Oral Health Impact Pro- to 25% are observed in specific groups such as postmenopausal ried out mainly in South Africa [11,12] and Nigeria [13] have con- cerned the BMS. These studies were methodologically biased and ALA: Alpha-Lipoic Acid file; IgE: Immunoglobulin E; Quantitative Sensory Testing (QST); did not distinguish between primary and secondary BMS. To our Introduction knowledge, no studies have been conducted on the BMS in French- Definition speaking Africa.

Classification Mouth Syndrome (BMS), or primary stomatodynia, as spontaneous The International Headache Society (IHS) defines Burning pain and burning sensation in an intact oral mucosa with no objec- Based on etiology as: [1]. The BMS is classified as follows: Primary, where etiology is unknown pathology has been evolving for at least 4 to 6 months. The pain tive clinical sign and no identifiable dental or medical cause Secondary, where the etiology is known [6,14]. is continuous, moderate to severe, often variable during the day: weak in the morning, it often increases during the day but rarely Based on symptoms as [6]: - • Type 1 BMS: Patients have no symptoms upon waking but ten disappears during meals. The most commonly affected area is disturbs patients’ sleep. It is not exacerbated by food intake and of symptoms progress throughout the day reaching its peak the tongue, but all areas of the oral cavity can be affected [1-5]. intensity by evening. Night-time symptoms are variable. It

Epidemiology and diabetes. is linked to systemic disorders like nutritional deficiency The prevalence of primary BMS is low, but studies report very variable numbers because of methodological biases related to • Type 2 BMS: Patients have continuous symptoms throughout the day and are symptomatic at night resulting in sleep- in studies, study design, and sampling selection bias [6]. The ac- sample size, the definition of the condition more or less restrictive to altered sleep pattern and is related to use of antidepres- tual prevalence is around 0.5% [7,8] in the general population but less nights. This type is associated with chronic anxiety due

sant drugs, which cause xerostomia. Citation: Papa Abdou Lecor., et al. “Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review”. Acta Scientific Dental Sciences 2.4 (2018) 26-32. Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review

27 • Type 3 BMS: Patients have intermittent symptoms through- Pathophysiology out the day with symptom free periods. Usually seen due

However, several types of injuries have been described. The pathophysiology of stomatodynia is not exactly known. to anxiety or allergic reactions especially to food allergens. Etiologies Neuropathic and peripheral microcirculation disorders

The etiologies of these nerve damage leading to stomatodynia Today, a consensus is established around a peripheral and/or are probably multiple. Neuropsychiatric, endocrine, immunologi- central neuropathic origin. At present, BMS is considered a painful cal, nutritional, infectious and iatrogenic causes have been suggest- condition involving neuropathic mechanisms, as evidenced by the ed [4] as the main factors associated with secondary BMS. These “burning” nature of pain. Patients diagnosed with primary BMS factors can disturb the oral environment and lead to sensory abnor- present the symptoms that are characteristic of trigeminal nerve malities (Table 1). The most common causes are oral mucosal ulcer- disorders (alteration of pain perception and neuronal transmis- ations, fungal infections, lichen planus, adverse drug reactions, and hormonal [6] a study of 123 patients initially diagnosed with primary BMS that sion,Some increased authors excitability have suggested of the vascular that peripheral system). nerve damage and vitamin deficiencies (Table 1). It was observed in 69% had subclinical thyroid abnormalities and could therefore be may be responsible for stomatodynia [2,3,5,24] considered secondary BMS [15]. Some oral dysesthesia may also be according to the origin of the pathology has been established: pe- . A classification [16], a general neu- - rological problem [2] associated with oral parafunctions (bruxism) ripheral neuropathy of small caliber oral fibres (50 - 60% of cas - , possibly related to toxic consumption such es), infra-clinical neuropathy of trigeminal major fibres (20 - 25% causes [17] [18-20], mate- tion (20 - 40% of cases). as alcohol or anxiety and psychological disorders, immunological of cases) and central deficiency in descending dopamine inhibi rials (resins, metals) used by the dentist [21]. Some autoimmune through exposure to dietary antigens At the peripheral level have been described in the affected mu- diseases such as Sjogren’s syndrome and systemic lupus erythema- cous membranes: tosus (Table 1) are also associated with oral burns mainly due to hyposialia [23]. • A lowering of the activation threshold of small diameter - ception; Psychological Local factors Systemic factors nerve fibres, responsible for the painful and thermal per factors • - Xerostomia (decreased Decreased levels bres, and morphological changes in epithelial and sub-epi- of vitamins B1, B2, A significant decrease in the density of epithelial nerve fi - B12, folate, iron, Anxiety salivary flow) generation and possibly responsible for painful sensations zinc thelial nerve fibres, recalling the mechanisms of axonal de Infections (Few mi- Diabetes Depression and dysgeusia [4,24,25]; crobes like Candida, • An increase in TRPV1 (transient receptor potential vanil- Enterobacter, Fusospi- loid 1) nociceptors and P2X3 receptors has also been de- rochetes, Helicobacter pylori and Klebsiella) by BMS. This increase has been linked to hypersensitivity Stomatitis under Thyroid hypofunc- Stress : scribed in the nerve fibres of mucous membranes affected prosthesis tion psychosocial, and neuropathic pain [4,26]. post-trauma- tic Electro-neuro-myographic studies have shown that patients Chronic trauma Menopause Inappropriate Sjogren’s syndrome Cancer phobia with BMS exhibited abnormalities of the masseterin and blink prostheses et al. [27] reported that reflexes, reflecting abnormalities in the large diameter trigeminal Parafunctional habits Systemic lupus unilateral anaesthesia of the lingual nerve leads to a reduction (cheek sucking, tongue erythematosus nerve fibre network. Gremeau-Richard., or even a homolateral or bilateral disappearance of symptoms, - tion tics...) and this only in a particular subgroup of patients, whose etiol- thrusting, bruxism, suc Oral mucosal conditions Various peripheral ogy of BMS has been linked to a peripheral cause. In this group, (erythema/erosion of or central neuropa- topical applications of clonazepam give the best results. In the whatever cause, atrophic thies (Parkinson’s other group, lingual nerve block does not improve or even worsen tongue, geographic disease, acoustic symptoms. In this group the etiology was linked to a central cause. tongue, lichen planus, neuroma, neuritis, pemphigoid, pemphigus) neuralgia...) At the central level, some studies have reported disturbances Gastritits, Gastroesopha- Drug therapies: of the sensory modulating pathways, including trigeminal nucleus angiotensin- (GRED) converting enzyme and striatum [26]. The alterations observed in the dopamine in- geal reflux disease (ACE) inhibitors hibitor system are similar to those seen in the early stages of Par- Allergic stomatitis (al- and angiotensin kinson’s disease [2]. Finally, the study of salivary and serum levels lergic or immunological receptor blockers, factors) antidepressants, of neurokinin A showed a decrease in serum levels of neurokinin hypoglycemic agents. [2]. A, reflecting an ineffective dopamine system in patients with BMS

Table 1: Different factors associated with oral pain Gustatory and salivary alterations sensations [4,6,7]. Taste to the anterior two third of the tongue is by the chorda Research into these associated factors is fundamental to differ- tympani branch of facial nerve and somatosensory is supplied by ential diagnosis between primary and secondary BMS. lingual nerve branch of trigeminal nerve. Chorda tympani hypo-

Citation: Papa Abdou Lecor., et al. “Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review”. Acta Scientific Dental Sciences 2.4 (2018) 26-32. Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review

28 function results in lingual nerve hyperfunction by disrupting the symptoms similar to neuropathic pain, such as tingling, itching, centrally-mediated equilibrium between the two [28]. Unilateral numbness, discomfort, etc [23,32]. The intensity of sensation varies from simple to severe pain. It is on average 5 to 8 on a VAS of burning pain on the contralateral anterior portion of the tongue, scale of 10 and is often underestimated by the medical profession. anesthesia of the chorda tympani nerve intensifies the perception suggesting the presence of central inhibitory interactions between Patients describe it as intense dental pain but of different quality taste and oral pain [28,29]. Damage to the chorda tympani or any [23,32]. Burns and other dysesthesias are mainly felt on the dorsal alteration in the gustative papillae releases this inhibition, and may side of the tongue and especially at the tip (glossodynia). But they may also be of interest to the lower lip, palate, retro-incisal area, to spontaneous pain, altered sensations of touch, subjective sensa- lead to an intensification of normal trigeminal sensations leading tions, of oral dryness and taste alterations (dysgeusia and phantom Symptoms may fade or disappear over time or persist without re- upper lip and more rarely, the jugal mucosa and floor of the mouth. tastes) [28,29]. mission for many years. Spontaneous remission was observed in 3% of patients 5 years after the onset of symptoms and a slight Individuals with high density of fungiform papillae present on improvement in less than 30% of cases [33]. Traditionally, pain is the anterior aspect of the tongue are known as supertasters and are described as daytime and does not interfere with sleep. more at risk for developing BMS [29,30]. Supertasters are mainly females who are able to perceive the bitter taste of a substance Oral pain may not be the only painful symptom, but many pa- - tients report other associated pain such as headaches, arthromy- tense burning sensation in the oral cavity, especially when stimu- algia [34] localized to the masticatory tract or neck; shoulders or called PROP (6-n-propylthiouracil) and also experience a more in lated with chili peppers [29,30]. suprahyoid muscles [35,36] and without evidence of a causal link being established, suggesting a general problem [37]. Xerostomia seen in BMS is more due to neuropathy than glandu- lar dysfunction [30]. It is noted that salivary content shows differ- Dysgeusia [30]. Persistent dysgeusias are found in 30-70% of patients with Psychologicalences but there disorders is no change in salivary quantity or flow BMS [38,39]. The main ones are bitter or metallic tastes [39] but alterations in the intensity of sweet and acidic perceptions are - also reported. Some foods worsen the symptoms, leading patients Many studies have found a significantly higher prevalence of de to avoid certain spicy and acidic foods (fruits), alcohol etc.. [4,24,31]. A low brain dopamine level is also associated with psy- pression, anxiety, irritability or somatization in patients with BMS chiatric disorders such as major depression. Nevertheless, these The tongue looks normal in most patients with BMS [38]. How- psychological disorders, which have long been mentioned as a pos- ever, Ching., et al. reported that 27% of BMS patients had geo- sible cause of stomatodynia, are probably the result of a chronic [24].

Salivarygraphic and Disorders fissured tongue compared to 11.5% in controls pathology whose management is difficult. Using reliable diagnostic BMS patients and patients with major depression [2,31]. - criteria, there was no statistically significant association between quent and concern about 46-67% of patients [7,9]. Changes in the Endocrine disorders Subjective complaints of oral dryness (xerostomia) are fre quality of saliva (electrolytes and proteins) that can be acidic or Menopause, whether surgical or physiological, is associated thick have also been reported [7,9]. This sensation is not often as- with higher prevalence of BMS. The mechanism is unclear but hor- sociated with objective salivary dysfunction (hyposialia). It may monal alterations may possibly affect the oral mucosa. Estrogen has be related to the adverse effects of psychotropic, anticholinergic, documented effects on oral mucosa, and deprivation may lead to antihistamine and diuretic drugs taken as part of treatment [39]. atrophic changes thereby altering stimulation of the nerve endings within the epithelium. Alternatively, atrophic epithelia may be more The evidence of neuropathic alterations led to the suggestion [2,4]. Thyroid hormones are involved in that salivary disorders could result from autonomic nervous sys- maturation and specialization of taste buds and studies have shown tem dysfunction [40]. However, few studies have attempted to prone to inflammation that thyroid hypofunction may be responsible for hypogeusia, for assess the function of the autonomic nervous system outside the bitter taste and for the release of inhibitions for sensitive trigeminal salivary system. sensation [2,15]. Clinical forms

Clinical features The clinical forms are varied both in the localization of symp- Pain toms which may concern only the tongue (glossodynia) or be felt The main complaint of stoma patients is pain which is generally in the other oral mucous membranes (stomatodynia) [25], in the bilateral and symmetrical and most often described as a prolonged level [41], in the description of symptoms (pain, paresthesia), as- burning sensation. However, the complaint can also be related to cephalic (headache) or extracephalic (fibromyalgia, arthralgia)

29 sociated disorders (taste and salivary), as well as in the temporal of the diagnostic approach avoids diagnostic errors. Additional course of pain [17,37] which can be continuous with a tendency to tests for peripheral or central neuropathy [2] were also proposed to complete the clinical diagnostic protocol (Table 4). patients), constant of equal intensity (type 2 [55%]) or intermittent increase gradually during the day (type 1, approximately 35% of (type 3 [10%]), and possibly related to an allergic component [17]. Local examination General examination - Measurement of salivary Blood tests: perfectly [32]. Nevertheless, this classification only models the temporal decay im • Complete blood cell count, VS, Oralflow ratecultures: (hyposialia) For bacte- CRP Quality of life rial, viral and fungal • Glucose level, glycosylated he- Studies using patient quality of life scales such as the Oral Health Infections moglobin (A1C) [42] have shown functional impairment of BMS patients [43] Inspection of mucous: • Nutritional factors (dosage vita- Impact Profile (OHIP) erythema, erosion, ul- mins B, zinc and folate) - , which also had high anxiety/depression scores, cerations, trauma, con- terioration in social relationships. There is also an impairment in • Thyroid function (dosage free significant emotional distress, loss of ability to take initiative, or de tact reactions with re- sleep quality compared to control subjects [44]. movable prostheses TSH, T3 and T4)

Table 2 summarizes the clinical description of primary BMS. Biopsy of tongue or oral • Immune function (Research of mucosa. antinuclear anti-Ro(SSA) and anti-La(SSB) antibodies, Total • Search for parafunction- serum IgE) though occurs in men as well. al habits Occurs most commonly, but not exclusively in females Patch tests: To check allergy to cer- • Seen in perimenopausal or postmenopausal women. Scintigraphy of the ma- tain foods, additives or even denture jor salivary glands materials. • of the oral soft tissues. Unexplained, usually persistent burning sensation or pain GERD • The diagnostic criteria for BMS are that pain episodes must Gastric reflux tests: To determine occur continuously for at least 4-6 months. They may last Table 3: Clinical and paraclinical investigations to for 12 years or more with an average duration of 3.4 years. diagnose BMS [2,5,6,15]. • Commonly affects the tongue presenting as glossodynia (painful tongue) and glossopyrosis (burning tongue). Tests Interest • Symptoms may vary from mild-to-severe but moderate Lingual electrogusto- Test the response to a progressively pain is seen frequently. metric increased thermal and gustatory stimulation compared to the sensations • Symptoms may appear early in the morning or develop of paresthesia; differentiate between later in the day. primary and secondary BMS; identify Quantitative Sensory peripheral neuropathy • Altered taste sensation such as bitter or metallic taste. Testing (QST) Evaluation of the • Oral mucosa appears apparently normal without any vis- - and distinguishes between peripheral Confirms neuropathic primary BMS ible changes. lation of supraorbital, and central origin mentalblink reflex and lingualby stimu • Xerostomia. nerves

• Evaluation of the density of epithelial and distinguishes central origin (no • PainfulGeographic teeth, and jaw fissured and temporomandibular tongue. joint. - Confirmsdensity neuropathicdisturbance) primary peripheral BMS phological changes • Loss of a comfortable jaw position and uncontrollable jaw innerve epithelial fibres, and and sub- mor (decreased epithelial density) and pe- tightness. origin due to small diameter fibres by biopsy mucosal neuropathy (decreased sub-epithelial • Headache, neck and shoulder pain. withepithelial BMS nerve fibres ripheral origin density)due to trigeminal fibre

• Increased parafunctional activity. Table 4: Complementary tests for peripheral or central • neuropathies [2].

• UsuallyDifficulty bilateral in speaking, but can nausea, be unilateral gagging as and well. dysphagia. Treatment and management

• Multiple mood and emotional disturbances. of other associated painful or non-painful factors make treatment Table 2: Clinical description of primary BMS [6,23,36,43]. The pathophysiological complexity of BMS and the prevalence

somatic and/or psychic effects according to the alleged etiology Investigations difficult. Numerous treatments have been proposed, targeting of the problem (antidepressants, analgesics, antiepileptics, anti- Knowledge of the pathophysiology and clinical symptoms al- fungal, antibacterial, antibacterial, sialagogues, antihistamines, lowed for a diagnostic approach based on clinical and paraclinical investigations [5,6,15] (Table 3). If the interrogation is evocative, - antihistamines, anxiolytics, antipsychotics, dietary supplements, hormones, etc). Several reviews of the literature [3,43] compiling vitamins and antioxidants, minerals and trace elements, capsaicin, that the oral examination does not show any abnormalities, a cer several randomized clinical trials evaluating the different treat- to be conducted before referring to a primary BMS. Systematization tain number of examinations and tests, summarized in table 3, are

30 ments for BMS have shown that, despite the many treatments used, Alpha-lipoic acid (ALA), a mitochondrial coenzyme as well as few treatments are truly effective in providing lasting relief of BMS pain, let alone its complete disappearance. There is currently no - a natural hepatic protector is powerful antioxidant able to exert gold standard. The various treatments used are as follows. rological properties. It has been studied in numerous trials (pre- an activity of protection of nerve fibres by its regenerative neu scribed systemically at daily doses of 600 - 800 mg/d). The results Topical (local) and systemic therapies are heterogeneous: some authors report up to 80% improvement Capsaicin is an alkaloid responsible for the burning sensation pro- and 10% resolved, while others do not detect any statistically duced by chilli peppers. It is capable of desensitizing TRPV1 calci- [56-60]. Combined with vitamin supple- - mentation, ALA does not give better results. In combination with significant differences icin results in a reduction of TRPV1 receptors in peripheral tissues, gabapentin, ALA gives better results than when used alone (70% um channel nociceptors and C-fibres. Prolonged exposure to capsa leading to long-term desensitization and symptom reduction. The improvement or resolution versus 55%). systemic use of capsaicin is associated with severe gastric pain, but Hormonal and behavioral therapies local use in mouthwash (250 mg/50 ml of water; 3 times/day) has Hormone replacement therapies have been proposed because average improvement of 3.2 on an VAS scale) without being able to stomatodynia often affect postmenopausal women, but these shown some efficacy (76% of cases reporting improvement, with an solve the disease successfully and durably [46,47]. studies have many methodological biases and do not allow for a [61]. Oral lidocaine has also been used topically to relieve the burning conclusion on the efficacy of such therapies sensation. Cognitive behavioral therapy has been proposed as an alter- native to pharmaceutical treatments. A weekly one-hour session Anticonvulsant drugs treatment of BMS. Clonazepam (Rivotril®), considered for its cen- are a drug class extensively tested in the improvement over the 6 months following therapy compared to of 12 to 15 weeks per week results in statistically significant placebo. However, the study is small in size, with no description propagation of electrical impulses in damaged areas of the central tral nervous system inhibitory action by specifically blocking the of the characteristics of the control and test groups, and the vi- nervous system. It was studied for topical application (tablet of 1 sual pain rating scale is not validated for the study of this type of mg 3 times/day) or systemic application (0.25 to 0.75 g/day) and pain. It should be noted that some studies report partial or total showed an improvement in both cases in about 70% of cases, with remission (with or without treatment) in about 50% of cases, with an average gain of 2.2 on an VSA scale [46,48-51]. In systemic use, spontaneous complete remission in 3 to 20% of cases, within 5 to side effects (heightening, drowsiness, increased dry mouth feeling, 7 years after onset of symptoms [62,63]. spasmophilia, euphoria) and the risk of addiction do not plead in fa- - Conclusion dynia [48,49,51]. On the other hand, in topical application, the side vor of a favorable risk-benefit balance for the treatment of stomato effects are less or even zero, which makes it a treatment of choice remains mysterious and further studies are needed to improve for stomatodynia [46,48,50]. For a few months now in France, the Despite significant advances in pathophysiology, primary BMS

- wandering for patients with BMS, emphasizing the importance of rologists. the management of this condition. There is significant diagnostic prescription of clonazepam has been exclusively reserved for neu diagnostic criteria and methodology. New tests based on the iden-

Gabapentin (Neurontin®) has also been used alone with refer- electrophysiology and immunohistochemistry) allow for the iden- ence to its action in the treatment of neuropathic pain [5], with dai- tification of subclinical changes detectable by fine methods (QST, - ly doses starting at 300 mg/d and increasing from 300 mg/d every [52]. tification of different subgroups and differential treatment strate the patient and often combine it with cognitive behavioral therapy. gies. Time must be taken to find the treatment that will relieve 2 daysPregabalin up to 2400 (Lyrica mg/d.®) performed The results better are not than significant gabapentin for the Acknowledgements treatment of BMS [53]. However, side effects and addiction risks do - None. ment of stomatodynia. not argue in favor of a favorable risk-benefit balance for the treat Conflict of Interest

Antidepressants and antipsychotics have often been studied to treat BMS because of their effect on neuropathic pain. Trazodone BibliographyThe authors declare no potential conflict of interests. (Oleptro®), Amisulpride (Solian® ®) and Ami- 1. ®) [54] were tested in turn, and did not show ef- ), Paroxetine (Deroxat 3rd edition (beta version)”. Cephalalgia 33.9 (2013): 629-808. IHS. “The International Classification of Headache Disorders, triptyline (Laroxyl mg/day. This study has a high rate of abandonment and loss of sight 2. Jääskelainen SK. “Pathophysiology of primary burning mouth ficacy greater than placebo, with the exception of Amisulpride at 50 (45%) [55]). syndrome”. Clinical Neurophysiology 123.1 (2012): 71-77.

31 3. De Moraes M., et al. “Randomized trials for the treatment of 19. Lynde CB., et al. “Burning mouth syndrome: patch test results burning mouth syndrome: an evidence-based review of the lit- from a large case series”. Journal of Cutaneous Medicine and erature”. Journal of Oral Pathology and Medicine 41.4 (2012): Surgery 18.3 (2014): 174-179. 281-287. 20. Kelava N., et al. “Oral allergy syndrome-the need of a multidis- 4. Gurvits GE and Tan A. “Burning mouth syndrome”. World Jour- ciplinary approach”. Acta clinica Croatica 53.2 (2014): 210- nal of Gastroenterology 19.5 (2013): 665-672. 219.

5. Lopez-Jornet P., et al. “Burning mouth syndrome: an update”. 21. Dutrée-Meulenberg RO., et al. “Burning mouth syndrome: Medicina Oral Patologia Oral y Cirugia Bucal 15.4 (2010): a possible etiologic role for local contact hypersensitivity”. e562-568. Journal of the American Academy of Dermatology 26.6 (1992): 935-940. 6. Scala A., et al. “Update on burning mouth syndrome: overview and patient management”. Critical Reviews in Oral Biology and 22. Marino R., et al. “Burning mouth syndrome: the role of contact Medicine 14.4 (2003): 275-291. hypersensitivity”. Oral Diseases 15.4 (2009): 255-258.

7. Bergdahl M and Bergdahl J. “Burning mouth syndrome: prev- 23. Grushka M., et al. “Burning mouth syndrome”. Advances in alence and associated factors”. Journal of Oral Pathology and Oto-Rhino-Laryngology 63 (2006): 278-287. Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 24. Ching V., et al. “Increased prevalence of geographic tongue in 28.8 (1999): 350-354. burning mouth complaints: a retrospective study”. Oral Sur- gery, Oral Medicine, Oral Pathology, and Oral Radiology 114.4 8. Kohorst JJ., et al. “The prevalence of burning mouth syndrome: (2012): 444-448. a population based study”. British Journal of Dermatology 172.6 (2015): 1654-656. 25. Penza P., et al. ‘‘Burning tongue’’ and ‘‘burning tip’’: the diagnostic challenge of the burning mouth syndrome”. The Clinical 9. Gorsky M., et al. “Burning mouth syndrome: a review of 98 Journal of Pain 26.6 (2010): 528-532. cases”. Journal of Oral Medicine 42.1 (1987): 7-9. 26. Yilmaz Z., et al. “Burning mouth syndrome as a trigeminal 10. Kohorst J., et al. “Incidence of burning mouth syndrome: a pop- - ulation-based study of Olmsted County, Minnesota”. Minnesota Journal small fibre neuropathy: Increased heat and capsaicin recep Medicine 97.9 (2014): 51. of Clinical Neuroscience 14.9 (2007): 864-871. tor TRPV1 in nerve fibres correlates with pain score”. 11. Maresky LS., et al. “Burning mouth syndrome. Evaluation of 27. Gremeau-Richard C., et al. “Effect of lingual nerve block on multiple variables among 85 patients”. Oral Surgery, Oral Medi- burning mouth syndrome (stomatodynia): a randomized cine, Oral Pathology, and Oral Radiology 75.3 (1993): 303-307. crossover trial”. Pain 149.1 (2010): 27-32.

12. Feller L., et al. “Burning Mouth Syndrome: Aetiopathogenesis 28. Eliav E., et al. “Evidence of chorda tympani dysfunction in pa- and Principles of Management”. Pain Research and Manage- tients with burning mouth syndrome”. Journal of the Ameri- ment (2017). can Dental Association 138.5 (2007): 628-633.

13. Chukwuneke F., et al. “Concurrent Presentation of Burning 29. Nasri-Heir H., et al. “The role of sensory input of the chorda Mouth Syndrome and Globus Pharyngis in Enugu, Nigeria: A tympani nerve and the number of fungiform papillae in burn- Ten-year Clinical Evaluation”. Oral Health and Preventive Den- ing mouth syndrome”. Oral Surgery, Oral Medicine, Oral Pa- tistry 12.3 (2014): 259-263. thology, Oral Radiology, and Endodontics 112.1 (2011): 65-72.

14. Maltsman-Tseikhin A., et al. “Burning mouth syndrome: will 30. Camacho-Alonso F., et al. “Fungiform papillae density in pa- better understanding yield better management?” Pain Practice Medic- 7.2 (2007): 151-162. ina Oral Patologia Oral y Cirugia Bucal 17.3 (2012): e362-366. tients with burning mouth syndrome and xerostomia”. 15. Femiano F., et al. “Burning mouth syndrome and burning 31. Schiavone V., et al. - mouth in hypothyroidism: proposal for a diagnostic and thera- Headache 52.6 “Anxiety, depression, and pain in burn peutic protocol”. Oral Surgery, Oral Medicine, Oral Pathology, (2012): 1019-1025. ing mouth syndrome: first chicken or egg”? Oral Radiology, and Endodontics 105.1 (2008): e22-27. 32. Braud A., et al. “Characteristics of pain assessed with Visual 16. Paterson AJ., et al. “Burning mouth syndrome: the relationship Analog Scale and questionnaire in burning mouth syndrome between the HAD scale and parafunctional habits”. Journal of patients: a pilot study”. The Journal of Oral and Facial Pain Oral Pathology and Medicine: Official Publication of the Interna- 27.3 (2013): 235-242. tional Association of Oral Pathologists and the American Acad- emy of Oral Pathology 24.7 (1995): 289-292. 33. Sardella A., et al. “Burning mouth syndrome: a retrospective study investigating spontaneous remission and response to 17. Lamey PJ., et al. “Type 3 burning mouth syndrome: psychologi- treatments”. Oral Diseases 12.2 (2006): 152-155. cal and allergic aspects”. Journal of Oral Pathology and Medi- cine: Official Publication of the International Association of Oral 34. Bergdahl BJ., et al. “Clinical study of patients with burn- Pathologists and the American Academy of Oral Pathology 23.5 ing mouth”. Scandinavian Journal of Dental Research 102.5 (1994): 216-219. (1994): 299-305.

18. Campisi G and Di Liberto C. “Food allergy in oral medicine. A 35. Svensson P and Kaaber S. “General health factors and den- review of the literature”. Minerva Stomatologica 52.7-8 (2003): ture function in patients with burning mouth syndrome 351-363. and matched control subjects”. Journal of Oral Rehabilitation 22.12 (1995): 887-895.

32 36. Corsalini M., et al. “Temporomandibular disorders in burning 52. Minguez Serra MP., et al. “Pharmacological treatment of burn- mouth syndrome patients: an observational study”. Interna- ing mouth syndrome: A review and update”. Medicina Oral Pa- tional Journal of Medical Sciences 10.12 (2013): 1784-1789. tologia Oral y Cirugia Bucal 12.4 (2007): E299-304.

37. Lamey PJ and Lewis MA. “Oral medicine in practice: burning 53. Lopez V., et al. “Marked response of burning mouth syndrome mouth syndrome”. British Dental Journal 167.6 (1989): 197- to pregabalin treatment”. Clinical and Experimental Dermatol- 200. ogy 34.7 (2009): e449-450.

38. Grushka M and Bartoshuk LM. “Burning mouth syndrome and 54. Sharav Y., et al. “The analgesic effect of amitriptyline on oral dysesthesia: taste injury is a piece of the puzzle”. The Cana- chronic facial pain”. Pain 31.2 (1987): 199-209. dian Journal of Diagnosis 17 (2000): 99-109. 55. Silvestre FJ., et al. “Burning mouth syndrome: a review and 39. Bergdahl M and Bergdahl J. “Perceived taste disturbance in update”. Revue Neurologique 60.10 (2015): 457-463. adults: prevalence and association with oral and psychological factors and medication”. Clinical Oral Investigations 6.3 (2002): 56. Femiano F. “Burning mouth syndrome (BMS): an open trial of 145-149. other therapies”. Minerva Stomatologica 51.9 (2002): 405- 40. Granot M and Nagler RM. “Association between regional idio- 409.comparative efficacy of alpha-lipoic acid (thioctic acid) with pathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints”. The Journal of Pain 57. Steele JC., et al. “Alpha-Lipoic acid treatment of 31 patients : Official Journal of the American Pain Society 6.9 (2005): 581- with sore, burning mouth”. Oral Diseases 14.6 (2008): 529– 587. 532.

41. Moisset X., et al. “Co-occurrence of pain symptoms and somato- 58. Cavalcanti DR and da Silveira FR. “Alpha lipoic acid in burn- sensory sensitivity in burning mouth syndrome: A systematic ing mouth syndrome– a randomized double-blind placebo- review”. PLoS ONE 11.9 (2016): e0163449. controlled trial”. Journal of Oral Pathology and Medicine 38.3 (2009): 254-261. 42. Larsson P., et al. “Reliability and validity of a Swedish version Acta Odontologica 59. Lopez-Jornet P., et al. Scandinavica 62.3 (2004): 147-152. mouth syndrome: a randomized, placebo-treatment study”. of the Oral Health Impact Proﬁle (OHIP-S)”. Journal of Oral Rehabilitation “Efficacy 36.1 of alpha (2009): lipoic 52-57. acid in burning 43. Lamey PJ., et al. “Vulnerability and presenting symptoms in burning mouth syndrome”. Oral Surgery, Oral Medicine, Oral 60. Marino R., et al. “Different therapeutic strategies for burning Pathology, Oral Radiology, and Endodontics 99.1 (2005): 48-54. mouth syndrome: preliminary data”. Journal of Oral Pathology and Medicine 39.8 (2010): 611-616. 44. Chainani-Wu N., et al. “A case-control study of burning mouth syndrome and sleep dysfunction”. Oral Surgery, Oral Medicine, 61. Tarkkila L., et al. “Oral symptoms at menopause-the role of Oral Pathology, Oral Radiology, and Endodontics 11.2 (2011): hormone replacement therapy”. Oral surgery, Oral medicine, 203-208. Oral pathology, Oral radiology, and Endodontics 92.3 (2001): 276-280. 45. Zakrzewska JM., et al. “Interventions for the treatment of burning mouth syndrome (Review)”. The Cochrane Database of Sys- 62. Keefe FJ. “Cognitive behavioral therapy for managing pain”. tematic Reviews 1 (2005): CD002779. The Clinical Psychologist 49.3 (1996): 4-5.

46. Woda A., et al. “A possible therapeutic solution for stomatodyn- 63. Scardina GA., et al. “Burning mouth syndrome: is acupunc- ia (burning mouth syndrome)”. The Journal of Oral and Facial ture a therapeutic possibility”? British Dental Journal 209.1 Pain 12.4 (1998): 272-278. (2010): E2.

47. Silvestre FJ., et al. “Application of a capsaicin rinse in the treatment of burning mouth syndrome”. Medicina Oral Patologia Volume 2 Issue 4 April 2018 Oral y Cirugia Bucal 17.1 (2012): e1-4. © All rights are reserved by Papa Abdou Lecor., et al. 48. Patton LL., et al. “Management of burning mouth syndrome: systematic review and management recommendations”. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and End- odontics 103.39 (2007): e1-13.

49. Zakrzewska J and Buchanan J. “Burning mouth syndrome”. BMJ Clinical Evidence 7 (2016): 1301.

50. Guarneri F., et al. - ing mouth syndrome: indications from benzodiazepine use”. Dermatologic Therapy “Contribution 21.2 (2008): of neuroinflammation S21–24. in burn

51. Woda A., et al. “Steroid Dysregulation and Stomatodynia (Burn- ing Mouth Syndrome)”. The Journal of Oral and Facial Pain 23.3 (2009): 202-210.

Citation: Papa Abdou Lecor., et al. “Burning Mouth Syndrome: Pathophysiology, Investigations and Management- A Review”. Acta Scientific Dental Sciences 2.4 (2018) 26-32.